Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neoplastic Stem Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2006

Neoplastic stem cells: a novel therapeutic target in clinical oncology.

Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long-term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of 'tumor stem cells' that exhibit a capacity for self-renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with 'more mature' tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy.

Animals↗
PubMed2005

Normal and neoplastic stem cells.

Stem cells are cells that at the single cell level both self-renew and give rise to differentiated progeny. Self renewal is the property that distinguishes stem cells and progenitors, and in the blood-forming system explains why haematopoietic stem cells (HSCs), not progenitors, are the only cells capable of providing rapid and sustained regeneration of the blood-forming system after ablation by cancer chemo- and radiotherapies. Cancer-free prospectively purified HSCs regenerate the haematopoietic system of patients as rapidly as a marrow or mobilized blood transplant, but without the risk of re-seeding the body with cancer cells. Further, purified allogeneic HSCs can establish donor-specific tolerance to subsequent tissue grafts. However, in contrast to widely-publicized reports of HSC plasticity, we have not been able to show transdifferentiation of HSC to muscle, heart, brain or gut, and conclude that rare cell fusions and incomplete purifications are likely explanations for the other published results. The ability to self-renew is also potentially dangerous, as poorly regulated self renewal is, we believe, a central lesion in all cancers. We have recently shown that myeloid leukaemias in mouse and human are often driven by rare leukaemia (cancer) stem cells which are at the progenitor stage of differentiation, but have activated the self-renewing cell division pathway normally used only by HSCs. Similar cancer stem cells have been isolated in other tumours.

Animals↗
PubMed1992

Variable expression of features of normal and neoplastic stem cells in patients with thrombocytosis.

Essential thrombocytosis (ET) is currently diagnosed by histopathologic assessment of the marrow after exclusion of a secondary cause or another myeloproliferative disorder. To evaluate the potential of more direct diagnostic methods, we compared the frequency and association of several abnormal features characteristic of neoplastic precursors in 32 patients presenting with platelet counts > 500 x 10(9)/l. Assays for erythropoietin (Ep)-independent erythroid progenitors were performed on all patients, determination of the cycling status of circulating progenitors on 27, and assessment of granulocyte clonality on 15. In most, but not all, patients deregulated progenitor turnover. Ep-independent progenitors and clonal granulocytes were concordant findings. The presence of polyclonal granulocytes and lack of evidence of abnormalities in Ep-dependence or progenitor cycling were also concordant findings in most, but not all patients. Thus, normal (i.e. polyclonal) granulocytes may be produced in occasional patients in spite of the presence of a neoplastic clone. Interestingly, one third of patients thought to have ET on the basis of blood and marrow histopathology showed no abnormalities previously associated with neoplastic progenitors. These findings suggest variability in dominance of the neoplastic clone in some ET patients and the potential utility of a multifaceted laboratory approach to investigate the underlying pathology in patients with thrombocytosis.

Adult↗
PubMed1993

The biology of normal and neoplastic stem cells in CML.

Chronic myeloid leukemia (CML) has long served as a prototype malignancy for basic as well as clinical studies aimed at developing curative cancer treatment protocols. Well established features of chronic phase CML are its origin in a pluripotent stem cell, a now well defined molecular genetic basis involving the creation of a BCR-ABL fusion gene and evidence of resultant abnormalities in the mechanisms that normally control primitive hemopoietic cell proliferation. We have recently shown how the long-term marrow culture system can be adapted to quantitate and characterize a very primitive cell type in normal blood and marrow samples, as well as their normal and leukemic counterparts in patients with CML. This system has also been used to dissect mechanisms of normal progenitor regulation and to identify specific anomalies affecting leukemic (CML) progenitors. Our studies show that cells detected by their ability to initiate long-term cultures (LTC) of leukemic cells (i.e., CML LTC-initiating cells or LTC-IC) are differently distributed between marrow and blood by comparison to LTC-IC in normal individuals and, although functionally similar in terms of the number and differentiation types of clonogenic cells they produce, CML LTC-IC exhibit defective self-maintenance. Phenotypically these primitive leukemic cells are heterogeneous; the majority display features of activated/proliferating cells but a significant proportion do not. We have also documented heterogeneity in primitive CML cell responses to two factors that specifically and reversibly arrest the cycling of primitive normal hemopoietic cells; i.e., TGF-beta and MIP-1 alpha, to which CML cells are normally responsive and abnormally unresponsive, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗
PubMed1985

Cell-mediated inhibition of tumor colony formation in agarose by resting and interleukin 2-stimulated human lymphocytes.

Human nonadherent peripheral blood mononuclear cells (PBMC) isolated from nonimmunized donors were preincubated for 18 h in medium alone or medium containing the lymphokine interleukin 2 and subsequently cocultured with tumor cells derived from malignant tumor cell lines or from fresh human tumors. The cell suspensions were subsequently inoculated into agarose; 14 days later, new tumor colony formation was determined. Although the different tumor cells displayed a wide range of sensitivity to the PBMC, in each instance, the number of colonies formed by the tumor cells exposed to the PBMC was consistently reduced relative to that of control cells. The inhibitory effect on the colony-forming cells was especially pronounced with PBMC preincubated with interleukin-2 and was dependent on the ratio of tumor cells to PBMC in the culture. This assay system provides an alternative to the standard 51Cr release assays in assessing the immunomodulatory effects of lymphokines and in quantitating the cytolytic or cytostatic activity of various effector cells against neoplastic stem cells from established cell lines and from heterogeneous cell preparations derived from fresh human tumors.

Cell Line↗
PubMed2005

Adult stem cells and cancer stem cells: tie in or tear apart?

Stem cell research is one of the new frontiers of medical science. Because of the unique self-renewable ability and powerful potential to differentiate, stem cells can be viewed as the mother of all cells in the body and have been investigated as a possible tool for reversing the degeneration and damage on organs. Recently, successful isolating cancerous stem cells from leukemia, breast and brain cancers provide a new target for eliminate cancer; however, it hints an increasing caution in using adult stem cells for organ repair. Cancerous stem cells share the same properties of self-renewal and differentiation with normal stem cells, with the addition of similar phenotype of adult stem cells isolated from the same tissue. Some believe that cancerous stem cells are derived from mutation of the normal stem cells, whereas others suspect it to be from different origins. Further investigation of the intrinsic factor underlying the behavior of adult stem cells and cancerous stem cells will shed light on both the fields of tissue engineering and cancer therapy. In this review, recent progresses in the studies of adult stem cells and cancerous stem cells are summarized to facilitate a better understanding and elicit much attention in this field.

Animals↗
PubMed2006

Stem cell enrichment approaches.

Adult somatic tissue, and the tumours that arise therein, are maintained by a small population of stem cells. In addition to the self-renewal potential and pluripotency, these stem cells express several phenotypic traits that can be used in isolation and enrichment strategies. Since most of the traits are not exclusive to the stem cells however, the resultant populations are typically heterogeneous and variable from one isolation to another. In this article, we review the strategies for isolation of stem cells, and the limitations thereof, with emphasis on mesenchymal tissue and bone tumours. The emerging evidence suggests that stem cell is not a distinct entity, but rather an indefinite state along a spectrum, characterized by phenotypic traits, epigenetic factors and the microenvironment.

Animals↗
PubMed2005

Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors.

Hepatocellular carcinoma is a chemoresistant cancer and a leading cause of cancer mortality; however, the molecular mechanisms responsible for the aggressive nature of this disease are poorly understood. In this study, we developed a new liver cancer mouse model that is based on the ex vivo genetic manipulation of embryonic liver progenitor cells (hepatoblasts). After retroviral gene transfer of oncogenes or short hairpin RNAs targeting tumor suppressor genes, genetically altered liver progenitor cells are seeded into the liver of otherwise normal recipient mice. We show that histopathology of the engineered liver carcinomas reveals features of the human disease. Furthermore, representational oligonucleotide microarray analysis (ROMA) of murine liver tumors initiated by two defined genetic hits revealed spontaneously acquired genetic alterations that are characteristic for human hepatocellular carcinoma. This model provides a powerful platform for applications like cancer gene discovery or high-throughput preclinical drug testing.

Animals↗
PubMed2002

E26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors.

Acute chicken leukemia retroviruses, because of their capacity to readily transform hematopoietic cells in vitro, are ideal models to study the mechanisms governing the cell-type specificity of oncoproteins. Here we analyzed the transformation specificity of 2 acute chicken leukemia retroviruses, the Myb-Ets- encoding E26 virus and the ErbA/ErbB-encoding avian erythroblastosis virus (AEV). While cells transformed by E26 are multipotent (designated "MEP" cells), those transformed by AEV resemble erythroblasts. Using antibodies to separate subpopulations of precirculation yolk sac cells, both viruses were found to induce the proliferation of primitive erythroid progenitors within 2 days of infection. However, while AEV induced a block in differentiation of the cells, E26 induced a gradual shift in their phenotype and the acquisition of the potential for multilineage differentiation. These results suggest that the Myb-Ets oncoprotein of the E26 leukemia virus converts primitive erythroid cells into proliferating definitive-type multipotent hematopoietic progenitors.

Alpharetrovirus↗
PubMed2004

Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm.

Epithelial mesenchymal transitions are a remarkable example of cellular plasticity. These transitions are the hallmark of embryo development, are pivotal in cancer progression, and seem to occur infrequently in adult organisms. The reduced incidence of transitions in the adult could result from restrictive functions of the microenvironment that stabilizes adult cell phenotypes and prevents plastic behavior. Multipotential progenitor cells exhibiting a mesenchymal phenotype have been derived from various adult tissues. The ability of these cells to differentiate into all germ layer cell types, raises the question as to whether mesenchymal epithelial transitions occur in the adult organism more frequently than presently appreciated. A series of cytokines are known to promote the transitions between epithelium and mesenchyme. Moreover, several transcription factors and other intracellular regulator molecules have been conclusively shown to mediate these transitions. However, the exact molecular basis of these transitions is yet to be resolved. The identification of the restrictive mechanisms that prevent cellular transitions in adult organisms, which seem to be unleashed in cancerous tissues, may lead to the development of tools for therapeutic tissue repair and effective tumor suppression.

Animals↗
PubMed2005

Biology of normal and acute myeloid leukemia stem cells.

The substantial understanding that has been gained over the past 5 decades of the biology of blood formation is largely due to the development of functional quantitative assays for cells at all stages of differentiation, from multipotential stem cells to mature cells. The majority of studies have involved the mouse because the ease with which repopulation studies can be carried out with this animal model allows the assay of complete lineage development from stem cells. In the past decade, advances in repopulation assays for human stem cells using xenotransplantation have greatly enhanced our understanding of human stem cell biology. Importantly, the xenotransplantation methodology has also been used to identify the cancer stem cell that initiates and sustains leukemic proliferation, providing key evidence for the cancer stem cell hypothesis. This hypothesis argues that cancer cells are functionally heterogeneous and hierarchically organized such that only specific cells are capable of sustaining tumor growth and continuously producing the cells that make up the bulk of the tumor. Recent studies have also brought into focus the importance of the intimate relationship between the stem cell (normal or leukemic) and its microenvironment. Coming into view are the molecular players involved in stem cell homing, migration, and adhesion, as well as the cellular components of the microenvironmental niche. Here we review recent studies that have begun, to elucidate the interplay between normal and leukemic human stem cells and their microenvironment.

Animals↗
PubMed1992

Early disappearance of murine plasmocytoma stem cells in long-term bone marrow culture.

Long-term bone marrow culture (LTBMC) was evaluated as a purging procedure in the murine plasmocytoma MOPC-315s system. MOPC-315s cells injected in Balb-c mice rapidly proliferate both in marrow and spleen, where macroscopic tumor colonies develop. A linear relationship between the number of injected cells and spleen colonies was observed, consistent with the presence of 1 clonogenic myeloma stem cell out of 1800 cells. In vitro, MOPC-315s cells are easily identifiable as rosette-forming cells (RFC+) with trinitrophenil acid (TNP) coated sheep red blood cells. When bone marrow (BM) cells containing 20-40% RFC+ were seeded in LTBMC, RFC+ rapidly decreased and were no longer detectable by day 14 of culture. Clonal Ig gene rearrangement was evident at time 0, but it was no more detectable later on. In addition, cells taken at days 14 and 21 of culture were no more tumorigenic when injected in vivo. The results suggest the efficacy of the LTBMC for the in vitro elimination of myeloma cells, including the neoplastic stem cells.

Animals↗